TY - JOUR
T1 - Genetically augmenting tau levels does not modulate the onset or progression of Aβ pathology in transgenic mice
AU - Oddo, Salvatore
AU - Caccamo, Antonella
AU - Cheng, David
AU - Jouleh, Bahareh
AU - Torp, Reidun
AU - LaFerla, Frank M.
PY - 2007/8
Y1 - 2007/8
N2 - The two hallmark pathologies of Alzheimer's disease (AD) are amyloid plaques, composed of the small amyloid-β (Aβ) peptide, and neurofibrillary tangles, comprised aggregates of the microtubule binding protein, tau. The molecular linkage between these two lesions, however, remains unknown. Based on human and mouse studies, it is clear that the development of Aβ pathology can trigger tau pathology, either directly or indirectly. However, it remains to be established if the interaction between Aβ and tau is bidirectional and whether the modulation of tau will influence Aβ pathology. To address this question, we used the 3xTg-AD mouse model, which is characterized by the age-dependent buildup of both plaques and tangles. Here we show that genetically augmenting tau levels and hyperphosphorylation in the 3xTg-AD mice has no effect on the onset and progression of Aβ pathology. These data suggest that the link between Aβ and tau is predominantly if not exclusively unidirectional, which is consistent with the Aβ cascade hypothesis and may explain why tauopathy-only disorders are devoid of any Aβ pathology.
AB - The two hallmark pathologies of Alzheimer's disease (AD) are amyloid plaques, composed of the small amyloid-β (Aβ) peptide, and neurofibrillary tangles, comprised aggregates of the microtubule binding protein, tau. The molecular linkage between these two lesions, however, remains unknown. Based on human and mouse studies, it is clear that the development of Aβ pathology can trigger tau pathology, either directly or indirectly. However, it remains to be established if the interaction between Aβ and tau is bidirectional and whether the modulation of tau will influence Aβ pathology. To address this question, we used the 3xTg-AD mouse model, which is characterized by the age-dependent buildup of both plaques and tangles. Here we show that genetically augmenting tau levels and hyperphosphorylation in the 3xTg-AD mice has no effect on the onset and progression of Aβ pathology. These data suggest that the link between Aβ and tau is predominantly if not exclusively unidirectional, which is consistent with the Aβ cascade hypothesis and may explain why tauopathy-only disorders are devoid of any Aβ pathology.
KW - Aging
KW - Alzheimer's disease
KW - Amyloid-β oligomers
KW - Neurofibrillary tangles
KW - Plaques
UR - http://www.scopus.com/inward/record.url?scp=34547464672&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547464672&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2007.04607.x
DO - 10.1111/j.1471-4159.2007.04607.x
M3 - Article
C2 - 17472708
AN - SCOPUS:34547464672
SN - 0022-3042
VL - 102
SP - 1053
EP - 1063
JO - Journal of neurochemistry
JF - Journal of neurochemistry
IS - 4
ER -